No abstract

Homeobox A5 (HOXA5) is a member of the homeobox gene (HOX) family, which plays an important role in the development of various malignant tumors. Here, we speculated that HOXA5 has an effect on cervical cancer development. In our study, we aimed to explore the role and molecular mechanism of HOXA5 in regards to the cell proliferation and apoptosis in cervical cancer. We found that expression levels of HOXA5 measured by RT-qPCR and western blot assays in cervical cancer cell lines and tissues were both significantly downregulated. We performed a gain-of-function experiment by the transfection with pcDNA.3.1-HOXA5 in ME-180 and HT-3 cells to overexpress HOXA5, and the caspase-3 activity measured by caspase-3 activity assay kit and cell apoptosis detected by flow cytometry were obviously promoted. Meanwhile, cell proliferation tested by BrdU assay, invasion determined by Transwell and cell viability tested by MTT were inhibited. Moreover, protein kinase B (AKT) was activated by incubation with SC79 (AKT activator; 1 µg/ml) after HOXA5 overexpression, and reversed the effect of HOXA5 overexpression on p27 expression. Additionally, significant elevation of AKT activation measured by western blot analysis abrogated the effect of HOXA5 on caspase-3 activity, cell apoptosis, proliferation, invasion and cell viability. Taken together, this study revealed that HOXA5 inhibits cervical cancer progression by regulating AKT/p27, proposing the potential role of HOXA5 in the prevention and treatment of cervical cancer.

Background The aim of this study was to describe the epidemiology of prelabour rupture of membranes (PROM) in China and to assess the association between clinical practice following the guidelines and early neonatal infections. Methods We conducted a prospective cohort study of 15926 deliveries in ShenZhen Baoan Women's and Children's Hospital, Xibei Women's and Children's Hospital and Chengdu Women's and Children's Hospital between August 1, 2017, to March 31, 2018. Clinical data were collected for each participant. The epidemiology of PROM was described. The association between PROM with early neonatal infectious outcomes and the influence of the implementation of the guideline on early neonatal infectious outcomes were assessed. Findings The incidence of PROM was 18•7%. PROM was showed to be a risk factor for neonatal infectious diseases (adjusted OR 1•92, 95%CI 1•49~2•49, p <0•0001), early-onset pneumonia (EOP) (adjusted OR 1•81, 95%CI 1•29~2•53, p =0•0006) and early-onset sepsis(EOS) (adjusted OR 14•56, 95%CI 1•90~111•67, p =0•01) for term neonates. For term neonates born from mother with PROM, induction of labor according to the guideline was a protective factor for neonatal diseases(adjusted OR 0•50, 95%CI 0•25~1•00, p =0•00498) and EOP(adjusted OR 0•32, 95%CI 0•11~0•91, p =0•03). For preterm neonates born from mother with PROM, using antibiotics according to the guideline showed to be protective for neonatal infectious diseases (adjusted OR 0•14, 95%CI 0•09~0•23, p <0•0001) and EOP (adjusted OR 0•08, 95%CI 0•04~0•14, p <0•0001). Interpretation Our study showed the risk of PROM for infectious diseases (including EOP and EOS) and the benefit of the usage of antibiotics according to the guideline for infectious diseases and EOP for preterm neonates. Funding National Natural Science Foundation of China, Capital Medical Development Research Fund of Beijing.

To find the risk of time thresholds of PROM for infectious diseases of term neonates. A multi-center prospective cohort study including pregnancies with PROM at term with a single fetus were conducted. Time thresholds of the duration from PROM to delivery were examined in 2-h increments to assess the rates of infectious neonatal diseases. 7019 pregnancies were included in the study. Neonatal pneumonia and sepsis were most frequent infectious diseases in neonates born from mother with PROM at term. Rates of early-onset pneumonia varied significantly when comparing length of time of PROM greater than 16 h vs. less than 16 h (for EOP in 3 days of life, adjusted OR 1.864, 95% CI 1.159 ~ 2.997, p = 0.010; for EOP in 7 days of life, adjusted OR 1.704, 95% CI 1.104 ~ 2.628, p = 0.016). Neonates born from mother of whom the length of time from PROM to delivery ≥ 16 h were at a higher risk of acquiring EOP.

Background Perinatal complications are common burdens for neonates born from mother with pPROM. Physicians and parents sometimes need to make critical decisions about neonatal care with short- and long-term implications on infant’s health and families and it is important to predict severe neonatal outcomes with high accuracy. Methods The study was based on our prospective study on 1001 preterm infants born from mother with pPROM from August 1, 2017, to March 31, 2018 in three hospitals in China. Multivariable logistic regression analysis was applied to build a predicting model incorporating obstetric and neonatal characteristics available within the first day of NICU admission. We used enhanced bootstrap resampling for internal validation. Results One thousand one-hundred pregnancies with PROM at preterm with a single fetus were included in our study. SNO was diagnosed in 180 (17.98%) neonates. On multivariate analysis of the primary cohort, independent factors for SNO were respiratory support on the first day,, surfactant on day 1, and birth weight, which were selected into the nomogram. The model displayed good discrimination with a C-index of 0.838 (95%CI, 0.802–0.874) and good calibration performance. High C-index value of 0.835 could still be reached in the internal validation and the calibration curve showed good agreement. Decision curve analysis showed if the threshold is > 15%, using our model would achieve higher net benefit than model with birthweight as the only one predictor. Conclusion Variables available on the first day in NICU including respiratory support on the first day, the use of surfactant on the first day and birthweight could be used to predict the risk of SNO in infants born from mother with pPROM with good discrimination and calibration performance.